Developed by: ANNA Specialty Practice Networks Acute Kidney Injury Fact Sheet Clinical Issues Overview • Overuse of medications, such as nonsteroidal anti- inflammatory drugs (NSAIDs, such as ibuprofen, With over 30 definitions of acute kidney injury (AKI) in pub- naproxen) and angiotension-converting enzyme (ACE) lished studies, there is no consensus among experts inhibitors. regarding how AKI is defined (Palevsky et al., 2013). Palevsky and colleagues (2013) describe AKI as a sudden Intra-Renal or Intrinsic loss of kidney function occurring over hours to days, result- Direct injury to the kidney or renal parenchyma due to fac- ing in fluid and electrolyte imbalance, retention of nitroge- tors, such as: nous waste products in the blood, and acid base irregular- • Cancer. ity. More specifically, AKI is defined as an increase in serum • Systemic Infection or sepsis. creatinine of 0.3 m/dL or higher within 48 hours, or an • Interstitial nephritis or allergic reaction to medications. increase in serum creatinine 1.5 times baseline within the • Scleroderma or other connective tissue disorder. prior 7 days, or a decrease in urine volume less than 0.5 • Damage to the renal tubules, such as glomerulonephri- mL/kg/hr for 6 hours (Kidney Disease: Improving Global tis, vasculitis, or thrombotic microangiography. Outcomes [KDIGO], 2012). Post-Renal In the United States, AKI has grown by 14% annually since Obstruction of the urinary tract leading to increase pressure 2001, with approximately 5% to 25% of all hospitalized in the Bowman’s capsule and reduced glomerular filtration patients diagnosed with AKI (Brown, Rezaee, Marshall, & rate (GFR) caused by: Matheny, 2016). AKI is associated with high mortality rates. • Enlarged prostate. The number of AKI hospital-related deaths increased • Cancer of bladder, cervix, or prostate. almost twofold, from 147,943 deaths in 2001 to 285,768 • Blood clot (thrombus). deaths in 2011 (Brown et al., 2016). Patients who develop • Kidney stones (renal calculi). AKI are at risk for adverse outcomes, such as cardiovascu- • Urethral strictures. lar events, pulmonary complications, and end stage renal disease (ESRD); however, it is important to note that Risk Factors Associated with AKI approximately 66% of all AKI episodes develop in the com- • Advanced age. munity, outside of the hospital setting (Harty, 2014). • Surgical procedures, especially cardiovascular surgery. Therefore, prevention, early recognition, and management • Sepsis. are essential to decrease poor health outcomes associated • Major trauma resulting in blood loss and muscle dam- with AKI. age. • Multiple organ dysfunction syndrome (MODS) seen in Causes and Risk Factors critically ill patients. • Exposure to radiocontrast agents. The etiologies of AKI are multifactorial and categorized as • Nephrotoxic drugs (NSAIDs, methotrexate, ACE pre-renal, intra-renal, or post-renal (Lameire, Van Biesen, & inhibitors). Vanholder, 2005). • Dehydration. Pre-Renal Signs and Symptoms Reversible kidney hypoperfusion associated with: • Hypotension. The clinical presentation of patients with AKI vary depend- • Volume depletion due to hemorrhage, diarrhea, dehy- ing on the severity and cause of AKI (Rahman, Shad, & dration, severe burns, or diuretics. Smith, 2012). Many patients with mild or moderate AKI are • Organ failure, such as pancreatitis and liver disease, asymptomatic (Rahman et al., 2012). According to the which causes shift of fluid in the abdomen. National Kidney Foundation (2019), patients with more • Heart failure or heart attack. severe AKI may have the following symptoms: • Severe allergic reactions. • Jugular venous distention. Acute Kidney Injury Fact Sheet Clinical Issues • Edema (peripheral, periorbital). increases, allowing plateau of the BUN and creatinine, • Dyspnea. then a gradual decline. Although significant improvement • Nausea and vomiting. in kidney function is observed in the first 1 to 2 weeks of • Fatigue. this phase, it may take up to 12 months for kidney func- • Confusion. tion to stabilize. Some patients do not recover and • Chest pain or pressure. progress to ESRD. The outcome of AKI is contingent • Back pain. upon the patient’s overall health, the severity of kidney • Decreased urine output (oliguria). damage, and the presence of complications and comor- • Seizure or coma in severe cases. bid conditions. With aggressive treatment, most patients achieve normal kidney function without complications. There are four phases of AKI. Depending on the phase of AKI, other clinical manifestations of AKI often present in crit- Diagnosis and Evaluation ically ill patients, including metabolic acidosis, hyperkalemia, hypophosphatemia, uremia, and azotemia. Although the The diagnosis of AKI is multifactorial, with an emphasis on severity of symptoms and the complexity of renal dysfunc- identifying the underlying cause. History and physical tion vary, the clinical course and manifestations of AKI gen- examination are important components in the diagnosis of erally progress over the following four phases (Dirkes, 2015; AKI, including assessment of volume status (Rhaman et al., Lewis, Dirksen, Heikemper, Bucher, & Harding, 2014): 2012). When conducting the physical examination, assess- • Onset Phase: Initial insult to kidney due to factors such ment of intravascular volume status and skin rash, which as blood loss, dehydration, burns, diabetes insipidos, or indicates systemic illness, is essential (Rahman et al., 2012). infection, resulting in a decrease in renal blood flow and Initial laboratory studies to assist in identifying the cause of tissue oxygenation 25% of normal and urine output less AKI include complete blood count, urinalysis, and kidney than 0.5 mL/kg/hr. This phase last hours to days. function studies, such as measurement of serum creatinine, • Oliguric Phase: The most common initial clinical mani- BUN, and fractional excretion of sodium (Rahman et al., festation of AKI is oliguria, defined as a reduction in urine 2012). According to Workeneh, Agraharkar, and Gupta output less than 400 mL/day. Oliguria is manifested with- (2017), the following laboratory and diagnostic studies are in 1 to 7 days of kidney injury. This phase typically lasts often performed to diagnose and determine the cause of 10 to 14 days but can last months in some cases. The AKI: longer the oliguric phase, the poorer the prognosis for • BUN and Creatinine: Elevation of creatinine and BUN the recovery of kidney function. However, approximately are hallmark indicators of kidney injury. The BUN-to-cre- 50% of patients will not experience oliguria, making diag- atinine ratio can exceed 20:1 in conditions that promote nosis difficult. In the oliguric phase, signs of fluid volume reabsorption of urea, such as large volume loss, which overload, such as edema, distended neck veins, hyper- suggests pre-renal AKI. tension, pulmonary edema, and heart failure, may occur. • Complete Blood Count: Used to detect infection, In addition to signs of volume overload, metabolic acido- chronic anemia, blood loss, or thrombotic microan- sis, hyperkalemia, hyperphosphatemia, and uremic giopathy. symptoms may also be present. • Urinalysis: Muddy, brown, granular casts; oxalate crys- • Diuretic Phase: In this phase, daily urine output is tals; and tubular casts in urine sediment may indicate approximately 1 to 3 liters but can reach as high as 5 acute tubular necrosis (ATN). Urine that is reddish-brown liters or more. The kidneys recover their ability to excrete in color indicates myoglobinuria or hemoglobinuria. waste but cannot concentrate the urine. Hypovolemia Further, renal tubular injury will result in proteinuria. and hypotension may occur due to massive volume Urinary red blood cells (RBCs) occur due to bleeding loss. Due to the loss of large volumes of fluid and elec- along the collecting system. RBC casts or dysmorphic trolytes, patients should be monitored for hyponatremia, RBCs in the urine are the result of glomerular inflamma- hypokalemia, and dehydration. This phase may last 1 to tion or glomerulonephritis. The presence of white blood 3 weeks. During the end of this phase, fluid and elec- cells (WBCs) or WBC casts suggests pyelonephritis or trolytes, acid-base balance, and waste product values interstitial nephritis. (blood urea nitrogen [BUN] and creatinine) start to nor- • Peripheral Smear: The presence of schistocytes sug- malize. gests hemolytic uremic syndrome and thrombotic • Recovery Phase: This phase begins when the GFR thrombocytopenic purpura. 2 Acute Kidney Injury Fact Sheet Clinical Issues Table 1. Staging of AKI Stage Serum Creatinine Urine Output 1 1.5 to 1.9 times baseline < 0.5 mL/kg/h for 6 to 12 hours OR ≥ 0.3 mg/dL (≥ 26.5 mmol/l) increase 2 2.0 to 2.9 times baseline < 0.5 mL/kg/h for ≥ 12 hours 3 3.0 times baseline < 0.3 mL/kg/h for X 24 hours OR OR Increase in serum creatinine to ≥ 4.0 mg/dL (≥ 353.6 mmol/L) Anuria for X 12 hours OR Initiation of renal replacement therapy OR In patients <18 years, decrease in eGFR to < 35 mL/min/1.73 m2 Source: KDIGO, 2012. • Fraction of Urinary Sodium (FENa): Measures the identified AKI when serum creatinine levels remained within percent of sodium excreted in the urine and is used to the normal range (Bongiovanni et al., 2015). determine pre-renal vs. ATN as the cause of AKI. This test is useful only in the presence of oliguria. In pre-renal KDIGO (2012) makes the following recommenda- conditions, FENa is usually less than 1%. In ATN, the tions for patients at risk for AKI: FENa is typically greater